Manifold Bio said it is seeking alternatives to transferrin-receptor strategies for delivering siRNAs and antibodies across the blood-brain barrier, aiming to avoid microvascular trapping and tissue off-targets seen with TfR approaches. The company’s platform is reportedly combining AI-designed receptor-ligand “portals” with in vivo screening to solve a “library-scale” search problem for brain-entry shuttles. On the mRNA therapeutics front, a Nature Biotechnology study described an mRNA vaccine approach that delays activation of an exogenous STING adjuvant using a synchronized lipid nanoparticle strategy. In mouse models, this design aims to enhance antitumor immunity while preserving production of vaccine antigens. Both advances focus on a recurring translational bottleneck—how to deliver immunostimulatory payloads to the right compartment without diminishing the therapeutic effect. The BBB delivery work targets the route into brain tissue, while the STING design targets the timing of innate immune activation.